From the Department of Surgery, West Virginia University/Charleston Division, Charleston Area Medical Center, 3200 MacCorkle Ave SE, Charleston, WV 25304 (A.R.D.); Department of Radiation Oncology, Inova Schar Cancer Institute, Fairfax, Va (C.B.J.); imagingwest, Hawthorne, NY (C.C.R.); Interventional Radiology Service (H.K., S.B.S., J.P.E.), Department of Epidemiology and Biostatistics (M.H., C.S.M.), and Department of Pathology, Precision Pathology Center (F.E.K., U.B.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Vascular & Interventional Radiology, Laboratory for Patient Inspired Engineering, Mayo Clinic, Scottsdale, Ariz (R.O.).
Radiology. 2023 Jan;306(1):279-287. doi: 10.1148/radiol.220158. Epub 2022 Aug 16.
Background The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE. Purpose To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations). Materials and Methods This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1-2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired tests. Results Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; = .02), IL-10 (0.2 vs 0.4 pg/mL; = .001), and IL-15 (1.9 vs 2.4 pg/mL; = .01) increased. In biopsy tissue, lymphocyte activation gene 3-positive CD4+ TILs (15% vs 31%; < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; < .001) and MDSCs (1% vs 5%; < .001) and higher programmed cell death protein (PD) 1-positive CD4+ TILs (59% vs 26%; = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; = .046). Conclusion Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1-positive tumor-infiltrating lymphocyte levels. © RSNA, 2022
背景 经动脉放射栓塞术（TARE）治疗乳腺癌肝转移（BCLM）对肿瘤免疫的影响尚不清楚，这阻碍了 TARE 候选患者的最佳选择。目的 确定 BCLM 患者经 PET/CT 评估的 TARE 反应是否与特定免疫标志物（细胞因子和免疫细胞群）相关。材料与方法 本前瞻性试点研究纳入了 23 名计划接受 TARE 的 BCLM 女性患者（2018 年 6 月至 2020 年 2 月）。在 TARE 前和 1-2 个月后采集外周血和肝肿瘤活检。使用基因表达研究和流式细胞术评估单核细胞、髓源抑制细胞（MDSC）、白细胞介素（IL）和肿瘤浸润淋巴细胞（TIL）水平，并使用免疫组化评估免疫检查点和细胞表面标志物水平。采用实体瘤改良 PET 反应标准评估治疗组织的完全缓解（CR）。经对数转换后，采用配对 检验比较 TARE 前后免疫标志物水平。采用 Wilcoxon 秩和检验或非配对 检验评估与 CR 的相关性。结果 20 名女性患者纳入研究。TARE 后，外周血中 IL-6（几何均数，1.0 比 1.6 pg/mL； =.02）、IL-10（0.2 比 0.4 pg/mL； =.001）和 IL-15（1.9 比 2.4 pg/mL； =.01）水平升高。在活检组织中，淋巴细胞激活基因 3 阳性 CD4+ TIL （15%比 31%； <.001）增加。20 名患者中有 8 名（40%[确切 95%CI：19，64]）达到 CR。CR 患者的外周血单核细胞（10%比 29%； <.001）和 MDSC（1%比 5%； <.001）水平较低，程序性死亡蛋白 1（PD）阳性 CD4+ TIL （59%比 26%； =.006）和肿瘤 PD-1 阳性染色（2%比 1%； =.046）水平较高。结论 TARE 的完全缓解与基线时细胞因子、单核细胞和髓源抑制细胞水平较低以及 PD-1 阳性肿瘤浸润淋巴细胞水平较高相关。 ©RSNA，2022
